Technical Field
This disclosure relates to chewable and sustained release compositions and dosage forms and to methods of preparing and using such compositions and dosage forms.
Description of the Related Art
A chewable pharmaceutical dosage is defined as a drug composition that retains certain drug release and taste properties even after it has been chewed into smaller fragments. Chewable pharmaceutical dosage forms are of particular interest for companion animal veterinary applications because the patients (e.g., dogs, cats, horses etc.) tend to chew any dosage form that is given orally. In human medicine, chewable dosage forms are preferred for young or senior patients who have difficulties in swallowing intact tablets or capsules.
Many drugs or pharmaceutically active ingredients require specific release kinetics such as a prolonged release, including drugs that have a short half-life and those that require sustained blood plasma levels. Sustained release formulations are developed to avoid multiple daily dosing and lack of, or reduced, patient compliance. Such formulations are also more preferably applied for patients on chronic medication.
Tablets are by far the most popular sustained release dosage form. Generally, sustained release tablets have been prepared in two ways: matrix and coated tablets. In a matrix tablet, the drug is usually mixed with a polymeric gelling material, which upon contact with water can form a thick layer of gel that slows down the diffusion of the drug while undergoing slow erosion. Both diffusion and erosion contribute to drug release. A coated tablet relies on small pores in the coating to control the drug release from its core.
The existing sustained release tablet compositions, whether matrix or coated, are not suitable as a chewable formulation, as they rely on matrix or coating to be intact for the drug release control. Chewing will destroy easily the integrity of the matrix or coating, and result in an uncontrolled drug burst or overdose and many times, unacceptable taste. Certain animals, such as cats, are extremely sensitive to taste and will not accept any dosage form voluntarily that has unfavorable taste. Accordingly, there is still a need for developing sustained release tablets that better retain the sustained release capability and certain taste masking property after being chewed or fragmented.
Other common dosage forms for oral administration to animal or human patients with swallowing limitation are multiparticulates that comprise a multiplicity of drug-containing particles whose totality represents the intended therapeutically useful dose of a drug. A multiparticulate formulation may be represented by other terms such as powders, granules, pellets, microspheres, minispheres, beadlets, sachets etc. It may be dosed as (1) dry powder which is administered orally and swallowed with liquid, (2) dispersed in a liquid and then swallowed, or (3) placed in a capsule. For the first and second methods of administration, large amounts of particles can be administered. For example, 5-10 grams of spherical pellets can be suspended in water and swallowed easily by a human patient. For animals such as horse, a multiparticulate formulation can be readily mixed with feed and consumed voluntarily, provided the taste is acceptable.
Numerous active ingredients require sustained release kinetics or prolonged release such as twice-a-day, preferably once-a-day, or ever more preferable once every 2-3 days. In such instances, use is made of so-called sustained release multiparticulate formulations. Known sustained release multiparticulate formulations rely almost exclusively on a thick coating system to provide a barrier to the drug release, i.e., “sustained release coating.” This is due to the greatly increased surface area of the small particles compared to a tablet. This great increase in surface area and fast dissolution have made sustained release particles or spheres almost impossible without the barrier coating (see, U.S. Patent Application Publication No. 2006/0153908, U.S. Pat. Nos. 5,188,841, 6,699,506, 6,897,205, and 6,436,438). The sustained release coating prevents the multiparticulate formulations form being used as a chewable dosage form because chewing would destroy the coating and result in drug burst and poor taste. Therefore, there is need for new multiparticulate compositions that can sustain certain chewing while maintaining a sustained release and certain taste masking properties.